ES2354976T3 - Fosfatasa alcalina placentaria para controlar la diabetes. - Google Patents

Fosfatasa alcalina placentaria para controlar la diabetes. Download PDF

Info

Publication number: ES2354976T3
Authority: ES; Spain
Prior art keywords: palp; glucose; human; active derivative; physiologically active
Prior art date: 2002-12-12
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

ES03796758T

Other languages

English (en)

Spanish (es)

Inventor

Zoltan Kiss

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

ZOLTAN LAB

ZOLTAN LABORATORIES

Original Assignee

ZOLTAN LAB

ZOLTAN LABORATORIES

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2002-12-12

Filing date

2003-12-05

Publication date

2011-03-21

2003-12-05 Application filed by ZOLTAN LAB, ZOLTAN LABORATORIES filed Critical ZOLTAN LAB

2011-03-21 Application granted granted Critical

2011-03-21 Publication of ES2354976T3 publication Critical patent/ES2354976T3/es

2023-12-05 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 77
102000002260 Alkaline Phosphatase Human genes 0.000 title claims description 4
108020004774 Alkaline Phosphatase Proteins 0.000 title claims description 4
102100024321 Alkaline phosphatase, placental type Human genes 0.000 claims abstract description 429
108010031345 placental alkaline phosphatase Proteins 0.000 claims abstract description 398
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 157
239000008103 glucose Substances 0.000 claims abstract description 146
238000002360 preparation method Methods 0.000 claims abstract description 82
239000003814 drug Substances 0.000 claims abstract description 33
239000003472 antidiabetic agent Substances 0.000 claims abstract description 24
230000003178 anti-diabetic effect Effects 0.000 claims abstract description 18
230000001603 reducing effect Effects 0.000 claims abstract description 13
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 140
102000004877 Insulin Human genes 0.000 claims description 70
108090001061 Insulin Proteins 0.000 claims description 70
229940125396 insulin Drugs 0.000 claims description 70
238000011282 treatment Methods 0.000 claims description 58
239000004365 Protease Substances 0.000 claims description 24
229940079593 drug Drugs 0.000 claims description 19
108010004032 Bromelains Proteins 0.000 claims description 18
235000019835 bromelain Nutrition 0.000 claims description 18
239000012634 fragment Substances 0.000 claims description 13
230000029087 digestion Effects 0.000 claims description 11
239000002504 physiological saline solution Substances 0.000 claims description 11
229940123208 Biguanide Drugs 0.000 claims description 7
239000003981 vehicle Substances 0.000 claims description 7
108091005804 Peptidases Proteins 0.000 claims description 6
102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 6
235000019419 proteases Nutrition 0.000 claims description 6
YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 claims description 5
229940123464 Thiazolidinedione Drugs 0.000 claims description 5
229940127003 anti-diabetic drug Drugs 0.000 claims description 5
229960002701 liraglutide Drugs 0.000 claims description 5
229940122199 Insulin secretagogue Drugs 0.000 claims description 4
239000003112 inhibitor Substances 0.000 claims description 4
239000002502 liposome Substances 0.000 claims description 3
230000003169 placental effect Effects 0.000 claims description 2
ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims 1
XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 claims 1
210000004369 blood Anatomy 0.000 abstract description 90
239000008280 blood Substances 0.000 abstract description 90
238000000034 method Methods 0.000 abstract description 47
238000011269 treatment regimen Methods 0.000 abstract description 21
208000001072 type 2 diabetes mellitus Diseases 0.000 abstract description 21
230000004584 weight gain Effects 0.000 abstract description 18
235000019786 weight gain Nutrition 0.000 abstract description 18
230000004580 weight loss Effects 0.000 abstract description 18
208000008589 Obesity Diseases 0.000 abstract description 13
235000020824 obesity Nutrition 0.000 abstract description 13
230000001939 inductive effect Effects 0.000 abstract description 6
241000282412 Homo Species 0.000 abstract description 5
241000124008 Mammalia Species 0.000 abstract description 4
230000000694 effects Effects 0.000 description 77
210000004027 cell Anatomy 0.000 description 72
238000002474 experimental method Methods 0.000 description 67
241000699670 Mus sp. Species 0.000 description 56
GZCGUPFRVQAUEE-IFLZFJRASA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxy(114C)hexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[14CH]=O GZCGUPFRVQAUEE-IFLZFJRASA-N 0.000 description 51
241001465754 Metazoa Species 0.000 description 47
239000002609 medium Substances 0.000 description 39
229920002527 Glycogen Polymers 0.000 description 32
229940096919 glycogen Drugs 0.000 description 32
238000011534 incubation Methods 0.000 description 27
150000002632 lipids Chemical class 0.000 description 27
241000699666 Mus <mouse, genus> Species 0.000 description 23
230000004153 glucose metabolism Effects 0.000 description 23
210000002966 serum Anatomy 0.000 description 22
230000015572 biosynthetic process Effects 0.000 description 21
230000001965 increasing effect Effects 0.000 description 21
ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 21
ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 20
229960001052 streptozocin Drugs 0.000 description 20
238000003786 synthesis reaction Methods 0.000 description 20
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
108090000623 proteins and genes Proteins 0.000 description 18
230000004936 stimulating effect Effects 0.000 description 18
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 17
210000001789 adipocyte Anatomy 0.000 description 17
238000007912 intraperitoneal administration Methods 0.000 description 17
238000000746 purification Methods 0.000 description 17
239000000203 mixture Substances 0.000 description 16
102000004169 proteins and genes Human genes 0.000 description 16
230000004060 metabolic process Effects 0.000 description 14
238000000926 separation method Methods 0.000 description 14
210000002950 fibroblast Anatomy 0.000 description 13
235000018102 proteins Nutrition 0.000 description 13
230000004190 glucose uptake Effects 0.000 description 12
239000007924 injection Substances 0.000 description 12
238000002347 injection Methods 0.000 description 12
108091003079 Bovine Serum Albumin Proteins 0.000 description 11
206010067584 Type 1 diabetes mellitus Diseases 0.000 description 11
210000000577 adipose tissue Anatomy 0.000 description 11
230000037396 body weight Effects 0.000 description 11
239000003795 chemical substances by application Substances 0.000 description 11
239000012091 fetal bovine serum Substances 0.000 description 11
230000007246 mechanism Effects 0.000 description 11
230000009471 action Effects 0.000 description 10
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
201000001421 hyperglycemia Diseases 0.000 description 9
210000001519 tissue Anatomy 0.000 description 9
102000004190 Enzymes Human genes 0.000 description 8
108090000790 Enzymes Proteins 0.000 description 8
108010092277 Leptin Proteins 0.000 description 8
239000000872 buffer Substances 0.000 description 8
230000001413 cellular effect Effects 0.000 description 8
210000001161 mammalian embryo Anatomy 0.000 description 8
238000004519 manufacturing process Methods 0.000 description 8
238000007920 subcutaneous administration Methods 0.000 description 8
230000004083 survival effect Effects 0.000 description 8
239000002753 trypsin inhibitor Substances 0.000 description 8
102000016267 Leptin Human genes 0.000 description 7
230000004700 cellular uptake Effects 0.000 description 7
230000007423 decrease Effects 0.000 description 7
230000004069 differentiation Effects 0.000 description 7
NRYBAZVQPHGZNS-ZSOCWYAHSA-N leptin Chemical compound O=C([C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CC(C)C)CCSC)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CS)C(O)=O NRYBAZVQPHGZNS-ZSOCWYAHSA-N 0.000 description 7
229940039781 leptin Drugs 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
150000004283 biguanides Chemical class 0.000 description 6
230000003247 decreasing effect Effects 0.000 description 6
238000000605 extraction Methods 0.000 description 6
238000004191 hydrophobic interaction chromatography Methods 0.000 description 6
230000002218 hypoglycaemic effect Effects 0.000 description 6
210000004185 liver Anatomy 0.000 description 6
230000009467 reduction Effects 0.000 description 6
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 6
208000002249 Diabetes Complications Diseases 0.000 description 5
229940100389 Sulfonylurea Drugs 0.000 description 5
239000013543 active substance Substances 0.000 description 5
GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
230000002641 glycemic effect Effects 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
239000007928 intraperitoneal injection Substances 0.000 description 5
238000005567 liquid scintillation counting Methods 0.000 description 5
210000003205 muscle Anatomy 0.000 description 5
210000000663 muscle cell Anatomy 0.000 description 5
230000003389 potentiating effect Effects 0.000 description 5
210000002027 skeletal muscle Anatomy 0.000 description 5
239000000126 substance Substances 0.000 description 5
206010012655 Diabetic complications Diseases 0.000 description 4
208000013016 Hypoglycemia Diseases 0.000 description 4
230000033228 biological regulation Effects 0.000 description 4
230000019522 cellular metabolic process Effects 0.000 description 4
238000007796 conventional method Methods 0.000 description 4
238000009826 distribution Methods 0.000 description 4
238000007446 glucose tolerance test Methods 0.000 description 4
239000003102 growth factor Substances 0.000 description 4
230000001404 mediated effect Effects 0.000 description 4
230000002093 peripheral effect Effects 0.000 description 4
210000002826 placenta Anatomy 0.000 description 4
210000005059 placental tissue Anatomy 0.000 description 4
238000001556 precipitation Methods 0.000 description 4
239000000047 product Substances 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
150000001467 thiazolidinediones Chemical class 0.000 description 4
238000005303 weighing Methods 0.000 description 4
238000004260 weight control Methods 0.000 description 4
SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical class COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 3
201000004569 Blindness Diseases 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
229920004011 Macrolon® Polymers 0.000 description 3
208000001145 Metabolic Syndrome Diseases 0.000 description 3
239000012614 Q-Sepharose Substances 0.000 description 3
201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 3
230000000996 additive effect Effects 0.000 description 3
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 3
229910052921 ammonium sulfate Inorganic materials 0.000 description 3
235000011130 ammonium sulphate Nutrition 0.000 description 3
238000005119 centrifugation Methods 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
235000005911 diet Nutrition 0.000 description 3
230000037213 diet Effects 0.000 description 3
201000010099 disease Diseases 0.000 description 3
230000000081 effect on glucose Effects 0.000 description 3
230000002255 enzymatic effect Effects 0.000 description 3
230000010005 growth-factor like effect Effects 0.000 description 3
229940088597 hormone Drugs 0.000 description 3
239000005556 hormone Substances 0.000 description 3
230000007774 longterm Effects 0.000 description 3
239000000463 material Substances 0.000 description 3
238000002483 medication Methods 0.000 description 3
229950004994 meglitinide Drugs 0.000 description 3
239000002547 new drug Substances 0.000 description 3
239000012071 phase Substances 0.000 description 3
230000035790 physiological processes and functions Effects 0.000 description 3
238000001243 protein synthesis Methods 0.000 description 3
239000007858 starting material Substances 0.000 description 3
230000000638 stimulation Effects 0.000 description 3
238000007910 systemic administration Methods 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
238000012360 testing method Methods 0.000 description 3
238000002560 therapeutic procedure Methods 0.000 description 3
230000014616 translation Effects 0.000 description 3
HBOMLICNUCNMMY-KJFJCRTCSA-N 1-[(4s,5s)-4-azido-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(C)=CN1C1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-KJFJCRTCSA-N 0.000 description 2
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
XZKIHKMTEMTJQX-UHFFFAOYSA-N 4-Nitrophenyl Phosphate Chemical compound OP(O)(=O)OC1=CC=C([N+]([O-])=O)C=C1 XZKIHKMTEMTJQX-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
102000016621 Focal Adhesion Protein-Tyrosine Kinases Human genes 0.000 description 2
108010067715 Focal Adhesion Protein-Tyrosine Kinases Proteins 0.000 description 2
208000018522 Gastrointestinal disease Diseases 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
208000001647 Renal Insufficiency Diseases 0.000 description 2
YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
229920002684 Sepharose Polymers 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
208000006011 Stroke Diseases 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
239000000654 additive Substances 0.000 description 2
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
230000002411 adverse Effects 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
238000010171 animal model Methods 0.000 description 2
230000000843 anti-fungal effect Effects 0.000 description 2
229940121375 antifungal agent Drugs 0.000 description 2
238000013459 approach Methods 0.000 description 2
230000008901 benefit Effects 0.000 description 2
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
230000004663 cell proliferation Effects 0.000 description 2
230000006790 cellular biosynthetic process Effects 0.000 description 2
239000000356 contaminant Substances 0.000 description 2
230000006378 damage Effects 0.000 description 2
230000034994 death Effects 0.000 description 2
230000007812 deficiency Effects 0.000 description 2
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
210000003754 fetus Anatomy 0.000 description 2
238000009472 formulation Methods 0.000 description 2
239000012737 fresh medium Substances 0.000 description 2
230000006870 function Effects 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
238000010348 incorporation Methods 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
230000003914 insulin secretion Effects 0.000 description 2
210000000936 intestine Anatomy 0.000 description 2
230000001788 irregular Effects 0.000 description 2
201000006370 kidney failure Diseases 0.000 description 2
230000037356 lipid metabolism Effects 0.000 description 2
238000013507 mapping Methods 0.000 description 2
230000008774 maternal effect Effects 0.000 description 2
XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 2
229960003105 metformin Drugs 0.000 description 2
201000001119 neuropathy Diseases 0.000 description 2
230000007823 neuropathy Effects 0.000 description 2
244000052769 pathogen Species 0.000 description 2
230000001575 pathological effect Effects 0.000 description 2
239000002953 phosphate buffered saline Substances 0.000 description 2
230000001766 physiological effect Effects 0.000 description 2
HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
230000035935 pregnancy Effects 0.000 description 2
GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical class C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 2
208000037821 progressive disease Diseases 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000000243 solution Substances 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
238000011421 subcutaneous treatment Methods 0.000 description 2
239000000725 suspension Substances 0.000 description 2
238000002054 transplantation Methods 0.000 description 2
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
238000000108 ultra-filtration Methods 0.000 description 2
XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
108010088751 Albumins Proteins 0.000 description 1
102000009027 Albumins Human genes 0.000 description 1
APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
208000002109 Argyria Diseases 0.000 description 1
206010003210 Arteriosclerosis Diseases 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
239000002126 C01EB10 - Adenosine Substances 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
208000002177 Cataract Diseases 0.000 description 1
208000021910 Cerebral Arterial disease Diseases 0.000 description 1
208000017667 Chronic Disease Diseases 0.000 description 1
DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical class C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 1
FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
208000002705 Glucose Intolerance Diseases 0.000 description 1
102000008214 Glutamate decarboxylase Human genes 0.000 description 1
108091022930 Glutamate decarboxylase Proteins 0.000 description 1
206010060378 Hyperinsulinaemia Diseases 0.000 description 1
238000012404 In vitro experiment Methods 0.000 description 1
206010022489 Insulin Resistance Diseases 0.000 description 1
108010044467 Isoenzymes Proteins 0.000 description 1
206010023379 Ketoacidosis Diseases 0.000 description 1
208000007976 Ketosis Diseases 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
101710113100 Membrane-bound alkaline phosphatase Proteins 0.000 description 1
206010030113 Oedema Diseases 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
102000008217 Pregnancy Proteins Human genes 0.000 description 1
108010035746 Pregnancy Proteins Proteins 0.000 description 1
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
238000012300 Sequence Analysis Methods 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
210000001744 T-lymphocyte Anatomy 0.000 description 1
IRLXSDZTLYOBQH-WOUKDFQISA-N [(2r,3s,4r,5r)-3,4-dihydroxy-5-imidazo[2,1-f]purin-3-yloxolan-2-yl]methyl dihydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(N=CN2C=CN=C22)=C2N=C1 IRLXSDZTLYOBQH-WOUKDFQISA-N 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
229960002632 acarbose Drugs 0.000 description 1
XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
230000004913 activation Effects 0.000 description 1
229960005305 adenosine Drugs 0.000 description 1
GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical class N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
210000000593 adipose tissue white Anatomy 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
229960003942 amphotericin b Drugs 0.000 description 1
208000007502 anemia Diseases 0.000 description 1
239000012984 antibiotic solution Substances 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
230000001363 autoimmune Effects 0.000 description 1
230000005784 autoimmunity Effects 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
230000008033 biological extinction Effects 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
238000009534 blood test Methods 0.000 description 1
235000021074 carbohydrate intake Nutrition 0.000 description 1
230000024245 cell differentiation Effects 0.000 description 1
230000008727 cellular glucose uptake Effects 0.000 description 1
230000005754 cellular signaling Effects 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
238000011210 chromatographic step Methods 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
230000001447 compensatory effect Effects 0.000 description 1
150000001875 compounds Chemical class 0.000 description 1
239000000470 constituent Substances 0.000 description 1
208000029078 coronary artery disease Diseases 0.000 description 1
230000001186 cumulative effect Effects 0.000 description 1
230000007547 defect Effects 0.000 description 1
230000002950 deficient Effects 0.000 description 1
238000001514 detection method Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
230000018109 developmental process Effects 0.000 description 1
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
229960003957 dexamethasone Drugs 0.000 description 1
238000000502 dialysis Methods 0.000 description 1
239000000539 dimer Substances 0.000 description 1
230000003292 diminished effect Effects 0.000 description 1
230000008034 disappearance Effects 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
210000003890 endocrine cell Anatomy 0.000 description 1
210000002919 epithelial cell Anatomy 0.000 description 1
210000004700 fetal blood Anatomy 0.000 description 1
235000013305 food Nutrition 0.000 description 1
235000012631 food intake Nutrition 0.000 description 1
230000037406 food intake Effects 0.000 description 1
238000001502 gel electrophoresis Methods 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
229960004580 glibenclamide Drugs 0.000 description 1
WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
229960004346 glimepiride Drugs 0.000 description 1
229960001381 glipizide Drugs 0.000 description 1
ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 1
150000002303 glucose derivatives Chemical class 0.000 description 1
230000009229 glucose formation Effects 0.000 description 1
230000010030 glucose lowering effect Effects 0.000 description 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
208000035474 group of disease Diseases 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
230000008821 health effect Effects 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
210000003494 hepatocyte Anatomy 0.000 description 1
230000013632 homeostatic process Effects 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
230000003451 hyperinsulinaemic effect Effects 0.000 description 1
201000008980 hyperinsulinism Diseases 0.000 description 1
229940126904 hypoglycaemic agent Drugs 0.000 description 1
229960003444 immunosuppressant agent Drugs 0.000 description 1
239000003018 immunosuppressive agent Substances 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
201000001881 impotence Diseases 0.000 description 1
230000001976 improved effect Effects 0.000 description 1
239000012535 impurity Substances 0.000 description 1
230000003993 interaction Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
210000004153 islets of langerhan Anatomy 0.000 description 1
208000017169 kidney disease Diseases 0.000 description 1
208000006443 lactic acidosis Diseases 0.000 description 1
150000002605 large molecules Chemical class 0.000 description 1
238000011542 limb amputation Methods 0.000 description 1
210000005229 liver cell Anatomy 0.000 description 1
238000011068 loading method Methods 0.000 description 1
208000018773 low birth weight Diseases 0.000 description 1
231100000533 low birth weight Toxicity 0.000 description 1
239000006166 lysate Substances 0.000 description 1
229920002521 macromolecule Polymers 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
229930182817 methionine Natural products 0.000 description 1
230000002297 mitogenic effect Effects 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004784 molecular pathogenesis Effects 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
238000004264 monolayer culture Methods 0.000 description 1
230000035772 mutation Effects 0.000 description 1
210000003098 myoblast Anatomy 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
238000012261 overproduction Methods 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
210000000496 pancreas Anatomy 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
239000011236 particulate material Substances 0.000 description 1
230000007119 pathological manifestation Effects 0.000 description 1
229940056360 penicillin g Drugs 0.000 description 1
208000030613 peripheral artery disease Diseases 0.000 description 1
239000003614 peroxisome proliferator Substances 0.000 description 1
238000002135 phase contrast microscopy Methods 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
229960005095 pioglitazone Drugs 0.000 description 1
229920002401 polyacrylamide Polymers 0.000 description 1
238000002264 polyacrylamide gel electrophoresis Methods 0.000 description 1
230000008092 positive effect Effects 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
210000000229 preadipocyte Anatomy 0.000 description 1
201000009104 prediabetes syndrome Diseases 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
230000000644 propagated effect Effects 0.000 description 1
230000017854 proteolysis Effects 0.000 description 1
239000013014 purified material Substances 0.000 description 1
238000004726 rapid resolution liquid chromatography Methods 0.000 description 1
238000010188 recombinant method Methods 0.000 description 1
230000029964 regulation of glucose metabolic process Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
229960002354 repaglinide Drugs 0.000 description 1
230000004044 response Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
229960004586 rosiglitazone Drugs 0.000 description 1
238000003345 scintillation counting Methods 0.000 description 1
230000000276 sedentary effect Effects 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
239000012679 serum free medium Substances 0.000 description 1
230000011664 signaling Effects 0.000 description 1
210000002363 skeletal muscle cell Anatomy 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017550 sodium carbonate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
239000012064 sodium phosphate buffer Substances 0.000 description 1
238000010532 solid phase synthesis reaction Methods 0.000 description 1
238000005063 solubilization Methods 0.000 description 1
230000007928 solubilization Effects 0.000 description 1
239000002904 solvent Substances 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
239000000758 substrate Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
150000003628 tricarboxylic acids Chemical class 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
230000003966 vascular damage Effects 0.000 description 1
230000000007 visual effect Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y301/00—Hydrolases acting on ester bonds (3.1)
- C12Y301/03—Phosphoric monoester hydrolases (3.1.3)
- C12Y301/03001—Alkaline phosphatase (3.1.3.1)
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Organic Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Diabetes (AREA)
Zoology (AREA)
Epidemiology (AREA)
Genetics & Genomics (AREA)
Wood Science & Technology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Endocrinology (AREA)
General Chemical & Material Sciences (AREA)
General Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
Biochemistry (AREA)
Hematology (AREA)
Obesity (AREA)
Microbiology (AREA)
Molecular Biology (AREA)
Biomedical Technology (AREA)
Dispersion Chemistry (AREA)
Biotechnology (AREA)
Gastroenterology & Hepatology (AREA)
Immunology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Child & Adolescent Psychology (AREA)
Emergency Medicine (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

ES03796758T 2002-12-12 2003-12-05 Fosfatasa alcalina placentaria para controlar la diabetes. Expired - Lifetime ES2354976T3 (es)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US441992		1989-11-28
US317916		2002-12-12
US10/317,916 US7048914B2 (en)	2002-12-12	2002-12-12	Placental alkaline phosphatase to control diabetes

Publications (1)

Publication Number	Publication Date
ES2354976T3 true ES2354976T3 (es)	2011-03-21

Family

ID=32506246

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ES03796758T Expired - Lifetime ES2354976T3 (es)	2002-12-12	2003-12-05	Fosfatasa alcalina placentaria para controlar la diabetes.

Country Status (6)

Country	Link
US (4)	US7048914B2 (de)
EP (1)	EP1733734B1 (de)
AT (1)	ATE480256T1 (de)
DE (1)	DE60334147D1 (de)
DK (1)	DK1572230T3 (de)
ES (1)	ES2354976T3 (de)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7048914B2 (en) *	2002-12-12	2006-05-23	Zoltan Laboratories	Placental alkaline phosphatase to control diabetes
EP1572230B1 (de) *	2002-12-12	2010-09-08	Zoltan Laboratories	Plazentäre alkalische phosphatase zur diabeteskontrolle
US20080279843A1 (en) *	2003-12-09	2008-11-13	Essential Skincare, Llc	Method For Improving Insulin Sensitivity By Administering an Inhibitor of Antitrypsin
US20110142817A1 (en) *	2004-02-04	2011-06-16	Pharmaaware Sepsis B.V.	Means and method for treating and/or preventing necrotizing enterocolitis
JP4999467B2 (ja)	2004-02-04	2012-08-15	ファルマアウェアセプシスビー．ブイ．	粘膜関門に存在するｌｐｓを解毒するためのアルカリホスファターゼの使用
US7557081B2 (en) *	2004-05-27	2009-07-07	Essential Skincare, Llc	Alpha-1-acid glycoprotein for the treatment of diabetes
US7695714B2 (en) *	2005-12-28	2010-04-13	Zoltan Laboratories Llc	Use of alkaline phosphatase to maintain healthy tissue mass in mammals
US20070149440A1 (en) *	2005-12-28	2007-06-28	Essential Skincare, Llc	Transferrin and transferrin-based compositions for diabetes treatment
US20070148140A1 (en) *	2005-12-28	2007-06-28	Zoltan Laboratories Llc	Compositions and methods to enhance viability and function of islet cells
EP1952823A1 (de) *	2007-01-30	2008-08-06	AM-Pharma B.V.	Verwendung von alkalischer Phosphatase bei der Behandlung eingeschränkter Nierenfunktion
US20090317372A1 (en) *	2008-06-20	2009-12-24	Zoltan Kiss	Small molecules for the reduction of high blood glucose level
US20100093603A1 (en) *	2008-07-17	2010-04-15	Kenneth Baker	Use of organic compounds
US20100215635A1 (en) *	2009-02-23	2010-08-26	Zoltan Kiss	Small molecules to induce weight loss or to reduce weight gain
US20130251701A1 (en) *	2010-10-22	2013-09-26	Zoltan Kiss Consulting	Alkaline phosphatase to correct insulin resistance, hyperinsulinemia, and dyslipidemia
US8679480B2 (en) *	2011-06-20	2014-03-25	Wisconsin Alumni Research Foundation	Method to inhibit neuropathic pain by intrathecal injection of protein phosphatases
ES2810813T3 (es)	2014-01-24	2021-03-09	Am Pharma Bv	Procesamiento para recuperación y purificación de una fosfatasa alcalina
CA2937328C (en)	2014-01-24	2022-09-27	Am-Pharma B.V.	Chimeric alkaline phosphatase-like proteins
EP3265119B1 (de)	2015-03-06	2023-10-11	Theriva Biologics, Inc.	Sichere und wirksame beta-lactamasedosierung für mikrobiomschutz
WO2018175413A1 (en)	2017-03-21	2018-09-27	Synthetic Biologics, Inc.	Alkaline phosphatase formulations
US11338020B2 (en)	2018-01-09	2022-05-24	Synthetic Biologics, Inc.	Alkaline phosphatase agents for treatment of neurodevelopmental disorders
ES3032290T3 (en)	2018-03-20	2025-07-16	Theriva Biologics Inc	Intestinal alkaline phosphatase formulations
US11654184B2 (en)	2018-03-20	2023-05-23	Theriva Biologics, Inc.	Alkaline phosphatase agents for treatment of radiation disorders
JP7660523B2 (ja)	2019-05-06	2025-04-11	セリバ・バイオロジクス・インコーポレイテッド	アルカリリン酸塩に基づいた癌治療
CA3142240A1 (en)	2019-06-03	2020-12-10	Synthetic Biologics, Inc.	Alkaline phosphatase formulations and uses thereof
EP3999637B1 (de)	2019-07-18	2025-04-02	Theriva Biologics, Inc.	Intestinale alkalische phosphatase-basierte behandlungen von stoffwechselstörungen
WO2022150034A1 (en) *	2021-01-06	2022-07-14	Zoltan Laboratories, Llc	Placental alkaline phosphatase for starting early treatment of cancer patients exhibiting no detectable loss of body and muscle weight as yet to prevent or reduce the loss of muscle proteins
US20240165209A1 (en) *	2021-02-16	2024-05-23	Zoltan Laboratories, Llc	Placental alkaline phosphatase for reducing the loss of red blood cells, white blood cells, and platelets in chemotherapy treated cancer patients

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4030995A (en) *	1976-07-13	1977-06-21	Sigma Chemical Company	Alkaline phosphatase isoenzyme determination
GB1594389A (en)	1977-06-03	1981-07-30	Max Planck Gesellschaft	Dressing material for wounds
IT1108964B (it) *	1978-01-20	1985-12-16	Sclavo Inst Sieroterapeut	Composizione adatta all'analisi della fosfatasi alcalina e metodo utilizzante la stessa
US4265233A (en)	1978-04-12	1981-05-05	Unitika Ltd.	Material for wound healing
DE3007226A1 (de)	1980-02-27	1981-09-10	Erich 2400 Lübeck Hofacker	Arzneikapsel
SU1138410A1 (ru)	1982-09-10	1985-02-07	Астраханский государственный медицинский институт им.А.В.Луначарского	Способ выделени термостабильной плацентарной щелочной фосфатазы
US4818540A (en)	1985-02-25	1989-04-04	Rutgers, The State University Of New Jersey	Transdermal fertility control system and process
JPS61277626A (ja)	1985-05-31	1986-12-08	Sugiura Shinyaku Kaihatsu Kenkyusho:Kk	ス−パ−オキシドジスムタ−ゼを高濃度に含有する胎盤エキスおよびその製法
DE3836971C1 (de)	1988-10-31	1990-05-17	Weck, Wolfgang, Dr.Med., 6990 Bad Mergentheim, De
JPH05506673A (ja)	1991-02-22	1993-09-30	アムジエン・インコーポレーテツド	迅速な創傷の治癒を促進するためのｇｍ―ｃｓｆ及びｇ―ｃｓｆの使用
CA2137275A1 (en)	1992-06-03	1993-12-09	Richard L. Eckert	Bandage for continuous application of biologicals
WO1995005455A1 (en) *	1993-08-13	1995-02-23	Rijksuniversiteit Te Groningen	Pharmaceutical composition comprising phosphatase or a derivative thereof
US5707624A (en)	1994-06-03	1998-01-13	The Regents Of The University Of Michigan	Treatment of Kaposi's sarcoma by inhibition of scatter factor
US5932779A (en)	1996-06-10	1999-08-03	Millennium Pharmaceuticals, Inc.	Screening methods for compounds useful in the regulation of body weight
US6005000A (en)	1996-08-22	1999-12-21	Oxis International, Inc.	5,5-Disubstituted-3, 4-dihydroxy-2(5H)-furanones and methods of use therefor
US6414036B1 (en)	1999-09-01	2002-07-02	Van Beek Global/Ninkov Llc	Composition for treatment of infections of humans and animals
US6627425B1 (en) *	2000-06-02	2003-09-30	Millennium Pharmaceuticals, Inc.	Human glucose-6-phosphatase molecules and uses thereof
US7011965B2 (en)	2001-03-09	2006-03-14	Regents Of The University Of Minnesota	Compositions and methods for stimulating wound healing and fibroblast proliferation
EP1572230B1 (de)	2002-12-12	2010-09-08	Zoltan Laboratories	Plazentäre alkalische phosphatase zur diabeteskontrolle
US7048914B2 (en) *	2002-12-12	2006-05-23	Zoltan Laboratories	Placental alkaline phosphatase to control diabetes
US7374754B2 (en)	2003-09-02	2008-05-20	Essential Skincare, Llc	Use of placental alkaline phosphatase to promote skin cell proliferation
US7695714B2 (en)	2005-12-28	2010-04-13	Zoltan Laboratories Llc	Use of alkaline phosphatase to maintain healthy tissue mass in mammals

2002
- 2002-12-12 US US10/317,916 patent/US7048914B2/en not_active Expired - Lifetime
2003
- 2003-05-20 US US10/441,992 patent/US7014852B2/en not_active Expired - Lifetime
- 2003-12-05 EP EP06018710.1A patent/EP1733734B1/de not_active Expired - Lifetime
- 2003-12-05 ES ES03796758T patent/ES2354976T3/es not_active Expired - Lifetime
- 2003-12-05 AT AT03796758T patent/ATE480256T1/de active
- 2003-12-05 DE DE60334147T patent/DE60334147D1/de not_active Expired - Lifetime
- 2003-12-05 DK DK03796758.5T patent/DK1572230T3/da active
2009
- 2009-01-28 US US12/361,310 patent/US7858085B2/en not_active Expired - Fee Related
2010
- 2010-11-17 US US12/948,146 patent/US8603464B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
US20040115185A1 (en)	2004-06-17
US7858085B2 (en)	2010-12-28
US7014852B2 (en)	2006-03-21
US20040120940A1 (en)	2004-06-24
EP1733734B1 (de)	2020-01-22
US7048914B2 (en)	2006-05-23
EP1733734A3 (de)	2011-09-28
ATE480256T1 (de)	2010-09-15
EP1733734A2 (de)	2006-12-20
US20090130080A1 (en)	2009-05-21
DE60334147D1 (de)	2010-10-21
US20110123513A1 (en)	2011-05-26
DK1572230T3 (da)	2011-01-03
US8603464B2 (en)	2013-12-10

Publication	Publication Date	Title
ES2354976T3 (es)	2011-03-21	Fosfatasa alcalina placentaria para controlar la diabetes.
JP4113778B2 (ja)	2008-07-09	真性糖尿病の治療方法
US8410081B2 (en)	2013-04-02	Treatment of cystic fibrosis
US6416794B1 (en)	2002-07-09	Methods and compositions for treating cataracts using substances derived from yeast or saltbush
CN107007606B (zh)	2021-10-26	一种用于干燥综合症预防及治疗的药物及其组合
KR20180095100A (ko)	2018-08-24	약제학적 조성물, 치료 방법 및 이의 용도
JP2019142907A (ja)	2019-08-29	トレハロースの非経口投与によるタンパク質凝集ミオパシーおよび神経変性疾患の治療
US7601688B2 (en)	2009-10-13	Methods of reducing hypoglycemic episodes in the treatment of diabetes mellitus
US7501116B2 (en)	2009-03-10	Placental alkaline phosphatase to control diabetes
US7947313B2 (en)	2011-05-24	Compositions for diabetes treatment and prophylaxis
WO2002038152A1 (es)	2002-05-16	Combinacion de aminas y compuestos de vanadio (iv)/(v) para el tratamiento y/o la prevencion de la diabetes mellitus
KR20220155910A (ko)	2022-11-24	RORα의 활성자 JC1-40을 포함하는 근감소증 예방, 개선, 또는 치료를 위한 약학적 조성물
US8895505B2 (en)	2014-11-25	Method of treatment of type 2 diabetes
ES2360235T3 (es)	2011-06-02	Sulfatidas para tratar trastornos autoinmunes.
CN112022862A (zh)	2020-12-04	磺酰脲类药物的抗衰老新用途
EP4487698A1 (de)	2025-01-08	Mikronährstoffzusammensetzung zur vorbeugung und umkehrung der proteinglykierung während oxidativem stress bei menschen
KR102206998B1 (ko)	2021-01-25	Lgi3 유래 펩타이드를 유효성분으로 포함하는 당뇨병의 예방, 치료, 또는 개선용 조성물
WO2024036044A1 (en)	2024-02-15	Compositions and methods for treating and preventing metabolic disorders
Hariprasad	2017	Pharmacological Evaluation of Novel Drugs in Rat Models of Peripheral Neuropathy
CN111228263A (zh)	2020-06-05	乙基甲基羟基吡啶苹果酸盐或其药物组合物，预防和/或治疗ⅱ型糖尿病的用途
Maria et al.	2012	Considerations Regarding the Therapeutic Conduct in Pregnancy Associated Diabetes Mellitus